Title:Diabetic Neuropathy: Update on Pathophysiological Mechanism and the Possible Involvement of Glutamate Pathways
Volume: 13
Issue: 5
Author(s): Nadia Hussain and Thomas E. Adrian*
Affiliation:
- Department of Physiology, College of Medicine and Health Sciences, UAE University, P.O. Box: 17666, Al Ain,United Arab Emirates
Keywords:
Diabetic neuropathy, autonomic neuropathy, pathophysiology, glutamate.
Abstract: Introduction: Diabetic neuropathy is a common complication of diabetes. It adversely affects
the lives of most diabetics. It is the leading cause of non-traumatic limb amputation. Diabetic
autonomic neuropathy can target any system and increases morbidity and mortality. Treatment begins
with adequate glycemic control but despite this, many patients go on to develop neuropathy which
suggests there are additional and unidentified, as yet, pathological mechanisms in place. Although several
theories exist, the exact mechanisms are not yet established. Disease modifying treatment requires
a more complete understanding of the mechanisms of disease.
Pathways Involved: This review discusses the potential pathological mechanisms of diabetic neuropathy,
including the polyol pathway, hexosamine pathway, protein kinase C, advanced glycation end
product formation, polyADP ribose polymerase, and the role of oxidative stress, inflammation, growth
factors and lipid abnormalities. Finally it focuses on how possible changes in glutamate signaling
pathways fit into the current theories.
Conclusion: Insights into the mechanisms involving gene expression in diabetic neuropathy can help
pinpoint genes with altered expression. This will help in the development of novel alternative therapeutic
strategies to significantly slow the progression of neuropathy in susceptible individuals and perhaps
even prevention.
